NanoMn®_COVID-19 A Prospective, Multicenter, Randomized, Placebo-controlled, Parallel-group, Double-blind Trial to Evaluate the Clinical Efficacy of NanoManganese® on Top of Standard of Care, in Adult Patients With Moderate to Severe Coronavirus Disease 2019 (COVID-19)

COVID-19 Pandemic Clinical Trial

Official title:

A Prospective, Multicenter, Randomized, Placebo-controlled, Parallel-group, Double-blind Trial to Evaluate the Clinical Efficacy of NanoManganese® on Top of Standard of Care, in Adult Patients With Moderate to Severe Coronavirus Disease 2019 (COVID-19)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05451654
• Other study ID #: 2020NanoMn-CT01
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: February 4, 2022
• Est. completion date: December 1, 2022

Study information

• Verified date: October 2023
• Source: Medesis Pharma SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective, multicenter, randomized (3:1), placebo- controlled, parallel-group, double-blind trial.

Patients will be randomized into two arms of treatment:

• Placebo + SoC (N=30)

• NanoManganese® + SoC (N=90)

Patients will be treated and followed-up for 10 days:

• Arterial oxygen partial pressure (PaO2) will be measured at baseline and at days 3, 5 and 10,

• Oxygen saturation, vital signs including respiration rate, pulse rate, blood pressure and body temperature, disease severity (7-point ordinal scale and NEWS2 score) will be measured at baseline and daily,

• Hematology and biochemistry measurements will be done at baseline and at day 3, 5 and 10,

• Pharmacokinetic (Blood Mn concentration) measurements will be done at baseline and at day 3, 5 and 10,

• Biomarkers will be measured at baseline and at day 3, 5 and 10. At the end of the 10-day treatment period, a follow-up visit will be planned between day 15 and day 22. The following.

assessments/examinations will be performed: oxygen saturation, vital signs including respiration rate and body temperature, disease severity (7-point ordinal scale and NEWS2 score), electrocardiogram (ECG), hematology, biochemistry, concomitant therapies, and adverse events.

Description:

120 patients will be enrolled in this study, they will be randomly assigned in 2 arms on a 3:1 ratio, 90 patients in the NanoManganese®

+ Standard of Care group and 30 patients in the placebo + Standard of Care group.

This study will be conducted in Brazil and will be conducted in around 8 investigational sites

The investigational products are :

Manganese sulfate monohydrate, MnSO4, H2O (NanoManganese®) will be administered using the microemulsion AONYS® technology. The product is mucoadhesive, it sticks to the mucosa of the cheeks on which it will be deposited and will not be swallowed.

The placebo (Pharmacopoeia soybean oil) will be administered using the same protocol and the same bottle.

Treatments :

NanoManganese® + standard of care group:

• NanoManganese®: administration of 2 mL twice a day (morning and evening) by depositing 1 mL in the gingivo-jugal groove of each cheek with the graduated pipette.

• Standard of care

Placebo + standard of care group:

• Placebo: administration of 2 mL twice a day (morning and evening) by depositing 1 mL in the gingivo-jugal groove of each cheek with the graduated pipette.

• Standard of care The treatments will be administered by the nurse. Duration of treatment: 10 days or until hospital discharge or until death.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: December 1, 2022
• Est. primary completion date: October 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male and female patient aged = 18 years

• Patient hospitalized with positive COVID-19, confirmed by a Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) or an antigen test done = 7 days before study entry

• Patient with at least 1 of the National Institutes of Health COVID- 19 clinical symptoms (Fever or chills, Cough, Shortness of breath or difficulty breathing, Fatigue, Muscle or body aches, Headache, New loss of taste or smell, Sore throat, Congestion or runny nose, Nausea or vomiting, Diarrhea) that appeared = 15 days before study entry

• Patient with a peripheral capillary oxygen saturation (SpO2) < 96%, or with an arterial oxygen partial pressure (PaO2) =65 mmHg, at study entry

• Female patient of childbearing potential must be willing to use an efficient birth control method during the study and until 3 months after IMP administration.

A woman is considered to be of childbearing potential if she is post menarche, has not reached a postmenopausal state (= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of

ovaries and/or uterus, tubal ligation). The following are acceptable contraceptive methods:

• Established use of oral, injected, or implanted hormonal methods of contraception - Intrauterine system or placement of an intrauterine device - Double barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam, gel, film, cream, or suppository - True abstinence [periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception]

• Male patient must be willing to use male contraception (condom) during the study, avoid donating semen during study and until 3 months after last dose of IMP administration.

• Patient must sign the informed consent form

• Patient who have or have not been vaccinated for COVID-19 (1, 2, 3 or 4 shots) can enter the study

Exclusion Criteria:

• Refusal to participate expressed by patient

• Pregnancy or breast-feeding

• Anticipated transfer to another hospital, which is not a study site within 72 hours

• Contraindication to Manganese supplementation

• Patient under Long-term oxygen therapy or invasive ventilation prior to COVID-19 infection

• Patient requiring Continuous Positive Airway Pressure (CPAP), high flow, or Non-Invasive Ventilation (NIV) and a SpO2 <92%

• Patient on invasive mechanical ventilation

• Patient with homozygotic sickle cell disease or methemoglobin.

• Patient receiving a biotherapy as a SoC for COVID-19

• Patient participating in another drug trial

• Patient under guardianship or prisoner

• Patient with a written order for restricted care

• Patient allergic to peanut or soja

• Patient under parenteral nutrition (with Mn in composition)

Related Conditions & MeSH terms

• COVID-19
• COVID-19 Pandemic

Intervention

Drug:
• Placebo
The administration of the treatment consists in a deposit in the gingivo-jugal groove of each cheek with a graduated pipette
• Experimental drug
The administration of the treatment consists in a deposit in the gingivo-jugal groove of each cheek with a graduated pipette

Locations

Country	Name	City	State
Brazil	Santa Casa BH	Belo Horizonte	Santa Efigenia

Sponsors (1)

Lead Sponsor	Collaborator
Medesis Pharma SA

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of the PaO2/FiO2 ratio	Change from baseline to D10 of the PaO2/FiO2 ratio in the NanoManganese® + SoC group and in the placebo+ SoC group.	10 days
Secondary	Proportion of patients with PaO2 > 65 mmHg	Proportion of patients with PaO2 > 65 mmHg at D3, at D5 and at D10, measured preferable after IP administration in the morning.	10 days
Secondary	Change of PaO2	Change between baseline and D10 of PaO2	10 days
Secondary	Evolution of respiratory rate over time	Evolution of respiratory rate over time	10 days
Secondary	Proportion of patients with SpO2 = 95%	Proportion of patients with SpO2 = 95% at D3, D5 and at D10,	10 days
Secondary	Change of SpO2	Change between baseline and D10 of SpO2,	10 days
Secondary	Incidence of oxygen use		10 days
Secondary	Duration of oxygen use		10 days
Secondary	Oxygen free days at D15-22 after inclusion		10 days
Secondary	Incidence of noninvasive support (high flow, CPAP, NIV) use		10 days
Secondary	Duration of noninvasive support (high flow, CPAP, NIV) use		10 days
Secondary	Noninvasive support (high flow, CPAP, NIV) free days during follow- up (between D15 and D22 after inclusion		10 days
Secondary	Incidence of invasive mechanical ventilation use,		10 days
Secondary	Duration of invasive mechanical ventilation use		10 days
Secondary	Invasive mechanical ventilation free days during follow-up (between D15 and D22 after inclusion)		10 days
Secondary	Time to improvement of 1 level on seven point ordinal scale	Higher scores indicate a worse outcome; - Not hospitalized, no limitation of activities; - Not hospitalized, limitation of activities; - Hospitalized, not requiring supplemental oxygen; - Hospitalized, requiring supplemental oxygen; - Hospitalized, on non-invasive ventilation or high flow oxygen devices; - Hospitalized, on invasive mechanical ventilation or ECMO; - Death	10 days
Secondary	Clinical status assessed by ordinal scale		10 days
Secondary	Proportion of patient transferred in ICU		10 days
Secondary	Description of ICU-free days during follow-up (between D15 and D22 after inclusion)		10 days
Secondary	Overall survival at day 22 and cause of death		10 days